For rectal and head and neck cancers, direct pO2 measurements have established a significant intratumoral hypoxic[unreadable] fraction. This is of great clinical significance as tumor hypoxia is thought to negatively influence cancer response to[unreadable] chemoradiation (CMT), a major treatment component for these tumors. However, current methods for assessing tumor[unreadable] hypoxia are limited by their invasive nature and associated sampling errors due to heterogeneity of intratumoral[unreadable] oxygenation. The focus of this project is the clinical evaluation of non-invasive imaging of global tumor hypoxia via[unreadable] positron emission tomography (PET) in patients with rectal and head and neck cancers.[unreadable] We propose to evaluate two hypoxia tracers conjugated with positron-emitting radioisotopes: 18F-FMISO and 124I-[unreadable] IAZGP. Given their different characteristics, difficult-to-predict pharmacokinetics, and possible disease and anatomyrelated[unreadable] influences, we will test them in these two tumor types and identify the optimal tumor-specific tracer. Therefore, the[unreadable] Specific Aims of RP4 are:[unreadable] I. To identify the optimal hypoxia tracer for PET imaging of locally advanced rectal cancer and head and neck cancers.[unreadable] 100 patients of each disease site will be studied, Each patient will be imaged with 18F-FMISOand 124I-IAZGP. The[unreadable] images will be evaluated in terms of image quality and prognostic value of treatment outcome.[unreadable] II. To correlate, in rectal cancer, global tumor hypoxia assessed by PET imaging with that assessed by direct pO2[unreadable] measurements using polarographic electrodes and IHC analysis of hypoxia-related proteins.[unreadable] We believe that these series of clinical studies will demonstrate the utility of PET hypoxia imaging and enhance the[unreadable] management of patients with rectal and head and neck cancers.